Lipid nanoparticles (LNPs) have become a clinically established platform for mRNA vaccine delivery, demonstrating significant potential in both infectious disease and cancer immunotherapy. However, excessive intracellular reactive oxygen species (ROS) can impair protein synthesis and compromise vaccine efficacy. To address this limitation, we developed an ionizable lipid incorporating a dopamine-derived moiety (DA lipid) for the formulation of ROS-scavenging LNPs. Comparative studies with oxidized control LNPs (ODA LNPs) revealed that DA LNPs exhibit superior intrinsic antioxidant activity, effectively mitigating intracellular ROS accumulation while supporting higher mRNA-derived protein expression. DA LNPs mediated transfection levels comparable to those achieved with ALC-0315 LNPs (ALC LNPs). In addition, DA LNPs induced stronger antigen-specific immune responses and more potent tumor suppression in a prophylactic mouse melanoma model compared to ODA LNPs. These results support the importance of redox modulation in optimizing mRNA vaccine performance and provide a rational design strategy for advanced nucleic acid delivery systems.

As a revolutionary cancer treatment strategy, immunotherapy has attracted great attention. However, the effect of immunotherapy such as immune checkpoint blockade (ICB) is usually limited by insufficient immune response in the body. Herein, a polycation-based magnetic nanocluster platform was developed to load therapeutic nucleic acids, which could achieve gene therapy-mediated ICB and efficient magnetic hyperthermia therapy (MHT). The silencing of immune checkpoints together with MHT-induced immunogenic cell death (ICD) effectively alleviated the immune escape of cancer cells and significantly enhanced the visibility of cancer cells to the immune system. This combined treatment strategy activated a strong adaptive anti-cancer immune response in vivo, greatly inhibiting tumor growth, metastasis and recurrence.